CD48 expression possible marker for mild asthma
medwireNews: CD48, a glycosylphosphatidylinositol-anchored receptor, may be a marker for diagnosing mild asthma, say researchers.
They found that in both its membrane (m) and soluble (s) forms CD48 was elevated in untreated patients with moderate asthma. And at optimal cutoff values of above 1482 pg/mL and above 1619 pg/mL for the two cohorts assessed, sCD48 differentiated mild asthma from no asthma with a respective 86.7% and 93.6% sensitivity, and 60.9% and 60.0% specificity
CD48 levels were significantly downregulated in patients with severe asthma, however, possibly as an indirect result of corticosteroid treatment or disease severity, making it less predictive in such patients, comments the team.
Francesca Levi-Schaffer (The Hebrew University of Jerusalem, Israel) and fellow researchers assessed blood leukocyte mCD48 expression and sCD48 in the serum of 77 individuals from Israel (IL) and 242 from the UK. The IL group comprised 21 patients with mild asthma, 21 with moderate asthma, 12 with severe asthma, and 23 healthy individuals without asthma, while the UK group had respective numbers of 31, 13, 183, and 15.
Flow cytometry analysis of blood leukocytes from patients in the IL group showed that mCD48 expression was significantly elevated 4.65-fold on the eosinophils of patients with moderate asthma compared with controls and 3.17-fold versus patients with mild asthma. There was no significant difference in expression on neutrophils or basophils, however.
Similarly, sCD48 levels were significantly increased an average 1.7-fold in the serum of mild asthma patients from both the IL and UK groups, compared with controls.
By contrast, sCD48 serum levels were significantly decreased in patients with severe asthma relative to patients with mild and moderate asthma in the UK cohort and were lower, although not significantly so, compared with patients with mild asthma in the IL cohort.
The researchers note in Allergy that sCD48 and mCD48 did not correlate with the presence of atopy, immunoglobulin E levels, or eosinophil numbers or percentages, which suggests CD48 is a specific marker of asthma rather than of atopy or eosinophilia.
mCD48 was predominantly expressed by eosinophils, rather than mast cells, in bronchial biopsies from patients with asthma, confirming previous murine findings. And the researchers found evidence that once formed sCD48 binds to its ligand CD244 on eosinophils as a “decoy receptor” blocking its interaction with CD48 and limiting subsequent cytokine activation.
Indeed, preincubating eosinophils with sCD48 and then with activating anti-CD244 monoclonal antibody resulted in decreased production of eosinophil peroxidase and interleukin-8, and, in turn, decreased Vav-1 phosphorylation.
“We have found CD244–CD48 interactions to be pivotal in the formation and activation of the [Allergic Effector Unit] between eosinophils and [mast cells], but this interaction may also be important in cross-talk between other inflammatory cells as well,” the researchers comment.
They suggest: “sCD48 could also modulate this interaction taking place in asthma and other allergic diseases.”
By Lucy Piper
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